Although several immunological reagents have been developed (ex: tumor infiltrating lymphocytes, antigen specific tumor vaccines, etc.) during the last few years which can recognize and kill melanoma cells and have the potential of curing melanoma patients, most patients are resistant to this form of therapy. This resistance is probably dependent upon a complexity of variables affecting the balance between activation of the immune system and growth of tumor cells in vivo and our limited understanding of them. My work is focused on analyzing variables potentially affecting this balance. Northern American melanoma patients represent a population significantly different from the North American Caucasian Population because of their different geographical ancestry. This difference is important because the polymorphisms associated with genetic variability may affect interpretation of in vitro data due to minor histocompatibility antigen mismatches. We also noted that tumors may stealth themselves from immune recognition using several mechanisms such as loss or decreased expression of HLA class I molecules (needed for recognition and killed by lymphocytes), variable expression of tumor associated antigens (the targets of immune recognition) both in culture conditions and in vivo or envelop antigen processing defects such as loss of function of transporter molecules. On the immune system side we are investigating the relationship between level of immune competence in tumor bearing and non bearing hosts and their ability to recognize and reject tumors (in vitro or in vivo) in natural conditions as well as during immune stimulation. Devotion of one investigator to the analysis of this variable may lead to information that, although not directly focused in the development and testing of new anti-cancer strategies, may be extremely valuable to the understanding of the biology of tumor rejection and provide a limited but significant support within the overall goals of the Tumor Immunology Section.